Globin family

To answer the first question, Lesk and Chothia examined in detail residues at structurally equivalent positions that are involved in helix-heme contacts and in packing the a helices against each other. After comparing the nine globin structures then known, the 59 positions they found that fulfilled these criteria were divided into 31 positions buried in the interior of the protein and 28 in contact with the heme group. These positions are the principal determinants of both the function and the three-dimensional structure of the globin family. 

A nice example to demonstrate this can be found in a paper from a group associated to the DGHP [67] The authors discovered a cDNA sequence for a novel protein of the globin family in databases of mice. Gene expression analyses showed that the novel protein was predominantly expressed in the brain - therefore the researchers called it Neuroglobin. They isolated Neuroglobin from mouse brain, cloned the respective cDNA and - also characteristic for the new biotech age - they filed a patent for Neuroglobin. 

Many examples of recurring domain or motif structures are available, and these reveal that protein tertiary structure is more reliably conserved than primary sequence. The comparison of protein structures can thus provide much information about evolution. Proteins with significant primary sequence similarity, and/or with demonstrably similar structure and function, are said to be in the same protein family. A strong evolutionary relationship is usually evident within a protein family. For example, the globin family has many different proteins with both structural and sequence similarity to myoglobin (as seen in the proteins used as examples in Box 4-4 and again in the next chapter). Two or more families with little primary sequence similarity sometimes make use of the same major structural... 

Before the evolution of protein function can be studied, functional differences first must be demonstrated between members of the family. At present, the best comparative biochemical data exist for classically studied protein families, such as the globin family and several families of digestive enzymes.3... 

Hankeln T, Ebner B, Fuchs C, Gerlach F, Haberkamp M, et al. 2005. Neuroglobin and cytoglobin in search of their role in the vertebrate globin family. J Inorg Biochem 99 110-119. 

Mammen PP, Shelton JM, Goetsch SC, Williams SC, Richardson JA, et al. 2002. Neuroglobin, a novel member of the globin family, is expressed in focal regions of the brain. J Histochem Cytochem 50 1591-1598. 

Maguid, S., Fernandez-Alberti, S., FerreUi, L., Echave, J. Exploring fhe common dynamics of homologous proteins. Application to the globin family, Biophys. J. 2005,89,3. 

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